Even by the isolated standards of rare diseases, Fabry disease is a lonely outpost. Only about 3,000 people around the world—1,000 of them in the United States-are being treated for the genetic disorder, which is caused by a deficiency in an enzyme involved in lipid metabolism.

Few people know what Fabry is, so specialists such as UAB nephrologist David Warnock, M.D., offer comparisons to more familiar conditions. "I like to make the analogy to diabetes," Warnock says. "Fabry affects the kidneys, heart, brain, gastrointestinal tract, skin, and nervous system. Like diabetes, it is a multisystem disease."

The greatest cause for concern, however, is kidney failure. Warnock led a UAB team that recently found that enzyme-replacement therapy, combined with an ACE inhibitor and angiotensin-receptor blocker (known as ACEI/ARB treatment), can help stop progressive loss of kidney function in Fabry patients. "Other published studies to date have shown continued loss of function, and we've been able to slow that loss to zero," Warnock says. "We can't return kidney function to normal, but we can stop further decline."

Expanding Options

This new treatment option should push back the boundaries of Fabry research. "Take kidney failure as an example," says Warnock. "Once we were able to offer dialysis, we had that as a safety net and could take more experimental approaches, which led to transplantation and rejection therapy. Enzyme-replacement therapy and combined ACEI/ARB treatment represent a safety net in Fabry disease, and we now can entertain new developments."

The most immediate hope may be the development of an oral agent, because the current regimen for enzyme-replacement therapy involves infusions every two weeks. "We also are looking at a Web-based survey to focus on cardiac issues in Fabry disease," Warnock says. "If you can stop the kidney involvement from getting worse, then you need to focus on the heart and the brain."

Patients are "highly motivated and grateful that we have something to offer them," Warnock notes. "That's the good news about studying a rare disease. The patient population is energized, and they participate in their care in a way you might not see in a more common disease."

Great Expectations

Warnock discovered this trait in 2001, when he met his first Fabry patient after a referral from an internal medicine physician. "It wasn't a difficult diagnosis; the disease is well described," Warnock recalls. "But the patient said he had a brother who was receiving experimental therapy at the National Institutes of Health, and he wanted to know if he could get that therapy at UAB. On that afternoon, the answer was no. But based on this patient's interest and enthusiasm, we became involved in the experimental treatment program.

"Our hope was to be able to intervene and stop progression, and we've been successful in doing that," Warnock says. "Now we can add Fabry disease to the list of treatable kidney diseases."